Investigation of the SH3BP2 Gene Mutation in Cherubism

Cherubism is a rare developmental lesion of the jaw that is generally inherited as an autosomal dominant trait. Recent studies have revealed point mutations in the SH3BP2 gene in cherubism patients. In this study, we examined a 6-year-old Korean boy and his family. We found a Pro418Arg mutation in the SH3BP2 gene of the patient and his mother. A father and his 30-month-old younger brother had no mutations. Immunohistochemically, the multinucleated giant cells proved positive for CD68 and tartrate-resistant acid phosphatase (TRAP). Numerous spindle-shaped stromal cells expressed a ligand for receptor activator of nuclear factor kB (RANKL), but not in multinucleated giant cells. These results provide evidence that RANKL plays a critical role in the differentiation of osteoclast precursor cells to multinucleated giant cells in cherubism. Additionally, genetic analysis may be a useful method for differentiation of cherubism.</p

The Role of Sphingosine Kinase 1/Sphingosine-1-Phosphate Pathway in the Myogenic Tone of Posterior Cerebral Arteries

AIMS: The goal of the current study was to determine whether the sphingosine kinase 1 (SK1)/sphingosine-1-phosphate (S1P) pathway is involved in myogenic vasoconstriction under normal physiological conditions. In the present study, we assessed whether endogenous S1P generated by pressure participates in myogenic vasoconstriction and which signaling pathways are involved in SK1/S1P-induced myogenic response under normal physiological conditions. METHODS AND RESULTS: We measured pressure-induced myogenic response, Ca(2+) concentration, and 20 kDa myosin light chain phosphorylation (MLC(20)) in rabbit posterior cerebral arteries (PCAs). SK1 was expressed and activated by elevated transmural pressure in rabbit PCAs. Translocation of SK1 by pressure elevation was blocked in the absence of external Ca(2+) and in the presence of mechanosensitive ion channel and voltage-sensitive Ca(2+) channel blockers. Pressure-induced myogenic tone was inhibited in rabbit PCAs treated with sphingosine kinase inhibitor (SKI), but was augmented by treatment with NaF, which is an inhibitor of sphingosine-1-phosphate phosphohydrolase. Exogenous S1P further augmented pressure-induced myogenic responses. Pressure induced an increase in Ca(2+) concentration leading to the development of myogenic tone, which was inhibited by SKI. Exogenous S1P further increased the pressure-induced increased Ca(2+) concentration and myogenic tone, but SKI had no effect. Pressure- and exogenous S1P-induced myogenic tone was inhibited by pre-treatment with the Rho kinase inhibitor and NADPH oxidase inhibitors. Pressure- and exogenous S1P-induced myogenic tone were inhibited by pre-treatment with S1P receptor blockers, W146 (S1P1), JTE013 (S1P2), and CAY10444 (S1P3). MLC(20) phosphorylation was increased when the transmural pressure was raised from 40 to 80 mmHg and exogenous S1P further increased MLC(20) phosphorylation. The pressure-induced increase of MLC(20) phosphorylation was inhibited by pre-treatment of arteries with SKI. CONCLUSIONS: Our results suggest that the SK1/S1P pathway may play an important role in pressure-induced myogenic responses in rabbit PCAs under normal physiological conditions

Effect of olmesartan and amlodipine on serum angiotensin-(1–7) levels and kidney and vascular function in patients with type 2 diabetes and hypertension

Background Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) [Ang-(1–7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-(1–7) levels as well as kidney and vascular function in patients with type 2 diabetes and hypertension. Methods This was a prospective, randomized, active comparator-controlled trial. Eighty participants with type 2 diabetes and hypertension were randomized to receive 20mg of olmesartan (N = 40) or 5mg of amlodipine (N = 40) once daily. The primary endpoint was changes of serum Ang-(1–7) from baseline to week 24. Results Both olmesartan and amlodipine treatment for 24weeks decreased systolic and diastolic blood pressures significantly by > 18mmHg and > 8mmHg, respectively. Serum Ang-(1–7) levels were more significantly increased by olmesartan treatment (25.8 ± 34.5pg/mL → 46.2 ± 59.4pg/mL) than by amlodipine treatment (29.2 ± 38.9pg/mL → 31.7 ± 26.0pg/mL), resulting in significant between-group differences (P = 0.01). Serum ACE2 levels showed a similar pattern (6.31 ± 0.42ng/mL → 6.74 ± 0.39ng/mL by olmesartan treatment vs. 6.43 ± 0.23ng/mL → 6.61 ± 0.42ng/mL by amlodipine treatment; P < 0.05). The reduction in albuminuria was significantly associated with the increases in ACE2 and Ang-(1–7) levels (r =  − 0.252 and r =  − 0.299, respectively). The change in Ang-(1–7) levels was positively associated with improved microvascular function (r = 0.241, P < 0.05). Multivariate regression analyses showed that increases in serum Ang-(1–7) levels were an independent predictor of a reduction in albuminuria. Conclusions These findings suggest that the beneficial effects of olmesartan on albuminuria may be mediated by increased ACE2 and Ang-(1–7) levels. These novel biomarkers may be therapeutic targets for the prevention and treatment of diabetic kidney disease. Trial registration: ClinicalTrials.gov NCT05189015.This research was funded by Daiichi Sankyo Co., Seoul, South Korea through a subcontract with SNUBH (Seongnam, Republic of Korea). The funding agency had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Development of a high yield purification process for the production of influenza virus vaccines

Production of influenza virus in animal cells has emerged as an alternative to conventional platforms such as egg-based production system. Animal cells, especially MDCK and VERO cell lines, are widely used as the primary production cell for influenza virus vaccine because of their high susceptibility to infection with various influenza viruses. Recently, a robust and reliable purification process was successfully developed for the production of quadri-valent HA proteins (from two strains of the type A virus and two strains of the type B virus) by using animal cell-based production system in Green Cross Corp., Korea. The UF/DF process, Benzonase treatment at high temperature as well as column chromatography strategy was optimized to maximize the final HA production yields. Benzonase treatment was conducted to reduce in hcDNA (host cell DNA) because hcDNA was main impurity for cell-based influenza virus vaccine. A simple and stable UF/DF process has been tested with membrane molecular weight cutoffs of 100 and 300 kDa as well as 0.2 and 0.45 um microfiltration membrane. Anion exchange chromatography (AEC) and size exclusion chromatography (SEC) were selected for acceptable reduction in hcDNA and HCP. AEC was used to separate hcDNA from virus at a salt concentration of 0.5 M sodium chloride. The HA yield through AEC & SEC combination process was sufficiently achieved under specific purification process condition. Overall, the amount of residual hcDNA was reduced to an acceptable level (10ng/dose) and the increased HA yield was maintained throughout the whole process. The performance, productivity and scalability of the purification process were successfully demonstrated in over 30 GMP batches using 4 different influenza virus strains

OMAE2004-51081 HULL FORMS FOR ICEBREAKING TANKERS

ABSTRACT The optimum design for an icebreaking tanker will depend on the trade route and the cargo delivery requirements. For example, the hull shape of a ship that spends almost all of its time operating in heavy ice can be optimized for low speed icebreaking conditions. In contrast, a ship that spends a small portion of its time in light ice that has been previously broken and the rest of its time in open water can be optimized for different requirements. The challenge for the designer is complicated by the observation that many ship design features that enhance powering performance in ice are detrimental to open water performance. This paper presents predictions of ship resistance in pack ice, level ice and open water for four tanker designs, which include a conventional hull with no modification for ice at all and three designs proposed for operation in Arctic ice conditions. The predictions of ship performance are based on model experiments carried out in Canada and Korea. The resistance of the four hulls in open water, two concentrations of pack ice and two level ice thicknesses are compared and discussed. Information of this sort is essential for developing the optimum ship design for a particular shipping route, given known profiles of open water, pack ice and level ice

The First Report of Fetal Alcohol Effect in a 12 Year-Old Child in Korea

We present the first report of fetal alcohol effect in a 12 year-old child in Korea. The mother had consumed 162 g of alcohol per week continuously during pregnancy. His first febrile seizure occurred before he was 1 year old, and became more frequent 2 years later. He started showing signs of right paraplegia when he was 3.5 years old and brain MRI revealed periventricular leucomalacia near the left ventricle. He was microcephalic and his growth was retarded. He was irritable, impatient, impulsive, and inattentive, and showed disinterest in school activities and aggressive and dangerous behavior. After the diagnosis of attention deficit/hyperactivity disorder was made, psychopharmacological treatment and family support was initiated. After 10 months, he still had intermittent ideas of reference, although the aggressive behavior, inattentiveness, and impulsivity had improved. Using this case study, we stress the importance of maternal alcohol history in patients with these characteristics

Android Fat Depot Is More Closely Associated with Metabolic Syndrome than Abdominal Visceral Fat in Elderly People

BACKGROUND: Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population. METHODS AND FINDINGS: As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9±8.6 years and 278 female, 76.0±8.8 years) with regional body composition data using Dual energy X-ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4±65.5 cm(2) and 126.9±55.2 cm(2) in men (P = 0.045) and 120.0±46.7 cm(2) and 211.8±65.9 cm(2) in women (P<0.01). Mean android and gynoid fat amount was 1.8±0.8 kg and 2.5±0.8 kg in men and 2.0±0.6 kg and 3.3±0.8 kg in women, respectively (both P<0.01). VAT area and android fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area. CONCLUSIONS: Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution

Titanium Oxide Nanotube Surface Topography and MicroRNA-488 Contribute to Modulating Osteogenesis

Understanding the biocomplexity of cell behavior in relation to the topographical characteristics of implants is essential for successful osseointegration with good longevity and minimum failure. Here, we investigated whether culture on titanium oxide (TiO2) nanotubes of various diameters could affect the behavior and differentiation of MC3T3-E1 cells. Among the tested nanotubes, those of 50 nm in diameter were found to trigger the expression of the osteoblast-specific transcription factors, sp7 and Dlx5, and upregulate the expression of alkaline phosphatase (ALP). Here, we report that miR-488 was significantly induced in osteoblasts cultured on 50 nm nanotubes and continued to increase with the progression of osteoblast differentiation. Furthermore, downregulation of miR-488 suppressed the expression levels of ALP and matrix metalloprotease-2 (MMP-2). This suppression of ALP transcription was overcome by treatment with the MMP-2 activator, bafilomycin A1. Collectively, these results suggest that 50 nm is the optimum TiO2 nanotube diameter for implants, and that modulation of miR-488 can change the differentiation activity of cells on TiO2 nanotubes. This emphasizes that we must fully understand the physicochemical properties of TiO2 nanotubes and the endogenous biomolecules that interact with such surfaces, in order to fully support their clinical application

Hemoperitoneum Caused by Hepatic Necrosis and Rupture Following a Snakebite: a Case Report with Rare CT Findings and Successful Embolization

We report the computed tomographic and angiographic findings in the case of a recently obtained successful clinical outcome after embolization of the hepatic artery in the case of a snakebite causing hemoperitoneum associated with hepatic necrosis and rupture with active bleeding

Potential Cause of Decrease in Bloom Events of the Harmful DinoflagellateCochlodinium polykrikoidesin Southern Korean Coastal Waters in 2016

Blooms of the ichthyotoxic dinoflagellateCochlodinium polykrikoidesare responsible for massive fish mortality events in Korean coastal waters (KCW). They have been consistently present in southern KCW over the last two decades, but they were not observed in 2016, unlike in the previous years. Despite extensive studies, the cause of this absence of this dinoflagellate bloom remains largely unknown. Thus, we compared physico-chemical and biological data from along the Tongyeong coast between 2016 and the previous four years (2012-2015). The averages of water temperature and salinity in August, 2016 were significantly (p&lt; 0.001) different from those in the previous years. The amount of Changjiang River discharge, which can affect the environmental conditions in the southern Korean coastal area via ocean currents, was larger than in the previous years, resulting in a reduction in the salinity level in August when blooms ofC. polykrikoidesusually occurred. Moreover, compared to previous years, in 2016, there was a weak expansion ofC. polykrikoidesblooms in the Goheung-Oenarodo area whereC. polykrikoidesblooms were annually initiated in KCW. Lastly, the strong winds from the typhoon Lionrock may also have contributed to the early termination of this dinoflagellate bloom. Together with these findings, the combination of these environmental conditions in 2016, unlike in previous years, may have inhibited the formation ofC. polykrikoidesblooms along the Tongyeong coast